Infrared spectroscopy is a powerful tool well-recognized as suitable for use in a variety of applications including cell biology, drug discovery, chemical composition analysis and material analysis. However, IR spectromicroscopy detection is limited by the signal-to-noise ratio achievable in a given IR spectromicroscopy system, while the main noise contribution in Mid-IR spectromicroscopy is thermal radiation background. To address this limitation, previous efforts have employed a very bright light source such as synchrotron radiation to achieve resolution sufficient for interrogating absorption or reflection spectra of very small samples such as a single biological cell, within a population of cells, small biomolecules, etc.
As known in the art, the infrared spectrum is conventionally divided into three sub-ranges, dubbed the near-, mid-, and far-IR regions, respectively. Near-IR is to be understood as corresponding to photons of light having a wavelength in a range from about 700 nm to about 3 um; mid-IR is to be understood as corresponding to photons of light having a wavelength in a range from about 3 um to about 15 um; and far-IR is to be understood as corresponding to photons of light having a wavelength in a range from about 15 um to about 1 mm.
However, requiring synchrotron light sources as a component of a Mid-IR spectromicroscopy system imposes undesirable consequences. Indeed, most synchrotron apparatuses are prohibitively large and/or expensive for most laboratory settings to obtain, maintain, and utilize. As a result, access to this technology is highly competitive and research progress rates are correspondingly slow. Furthermore, many conventional approaches that use synchrotron or other very bright light sources have the propensity to destroy biological samples, which is an undesirable limitation especially where sample availability is limited, such as commonly is the case with clinical tissue samples, national security applications, etc. Further still, synchrotron or other bright light-source IR spectromicroscopy systems typically operate at or above room temperature, which increases thermal radiation background which at room temperature makes single photon detection impossible simply by overloading photon sensitive detectors.
Moreover, all life-important chemical interaction are situated in the mid-to-far infrared energy range (e.g. at around a temperature of about 300K, or an energy of ˜30 meV). Mid-IR and Far-IR spectroscopy are powerful tools for analysis of chemical compositions and chemical bonds, for biomedical, chemical or material science purposes. Raman scattering of visible light is the conventional tool for chemical microspectroscopy. Currently Raman scattering of visible light (where single photon detectors are available) is in use to get information about energy levels in the Mid-IR region, but, to get single molecular sensitivity (ability to detect presence of single molecule of interest inside the sample) these applications required destructive visible light intensities unsuitable for use in measuring Raman spectra of live or otherwise delicate samples. Finally, cross sections of direct infrared photon interactions like absorption, resonant scattering, etc. are 6 to 12 orders of magnitude larger than the cross section of Raman scattering of visible light photons.
Accordingly, it would be beneficial to provide new systems, methods, and/or computer program products enabling infrared spectromicroscopy such that, particularly in the mid-IR and far-spectral regions, single-photon sensitive Mid-IR spectromicroscopy techniques can be employed to minimize radiational load on the system and permit mid-IR and far-IR emission study of small and/or delicate samples such as living cells, small biomolecules, etc. Potentially, a single molecular detection can be achieved.